Requirements for Registration,

Updating and Results Reporting for ClinicalTrials.gov

Karla Damus PhD MSPH MN BSN RN FAANAdministrator, BMC/BUMC Clinicaltrials.gov and

Clinical Research Education

OHRA, CRRO, CTSI

damusk@bu.edu, 358 7382

Office of Human

Research Affairs

Objectives

• Provide a brief history, scope and mission of ClinicalTrials.gov

• Explain the role of the ICMJE on the registration process and data

sharing

• Discuss best practices and tips for registering, updating and posting

results on clinicaltrials.govUnderstand how to gain access to CTgov as a new user, start a new record, and

add users

Describe the role of the RP (responsible party) and institution/sponsor

Present when and how to update/edit existing records

Provide an overview of results reporting and submitting documents

• Discuss the penalties and enforcement for noncompliance

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Why is Trial Registration Important?

• The registration of all interventional trials is considered to be a scientific, ethical and moral

responsibility because:

• There is a need to ensure that decisions about health care are informed by all of the available

evidence

• It is difficult to make informed decisions if publication bias and selective reporting are present

• The Declaration of Helsinki (1964) states that "Every clinical trial must be registered in a publicly

accessible database before recruitment of the first subject".

• Improving awareness of similar or identical trials will make it possible for researchers and funding

agencies to avoid unnecessary duplication

• Describing clinical trials in progress can make it easier to identify gaps in clinical trials research

• Making researchers and potential participants aware of recruiting trials may facilitate recruitment

• Enabling researchers and health care practitioners to identify trials in which they may have an

interest could result in more effective collaboration among researchers. The type of collaboration

may include prospective meta-analysis

• Checking study design and outcome measures as part of the registration process may lead to

improvements in the quality of clinical trials by making it possible to identify potential problems

(such as problematic randomization methods) early in the research process

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What is ClinicalTrials.gov?

• ClinicalTrials.gov is a Web-based resource that provides patients, their family members,

health care professionals, researchers, and the public with easy access to information on

publicly and privately supported clinical studies on a wide range of diseases and

conditions. It is searchable like PubMed and also maintained by the NLM at NIH.

• Studies are generally submitted to the Web site (registered) when they begin, and the

information on the site should be updated throughout the study.

• For some but not all studies, results are submitted after the study ends. This Web site

and database of clinical studies is commonly referred to as a "registry and results

database."

• ClinicalTrials.gov contains information about clinical studies in human volunteers. Most of

the records describe clinical trials (also called interventional studies).

• A clinical trial is a research study in which human volunteers are prospectively assigned

to interventions (for example, a medical product, behavior, or procedure) based on

a protocol (or plan) and are then evaluated for effects on biomedical or health outcomes.

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ClinicalTrials.gov

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https://clinicaltrials.gov/ct2/resources

International Clinical Trials Registry Platform (ICTRP)

WHO ICTRP-The main aim of the WHO ICTRP is to facilitate the prospective registration of the WHO Trial

Registration Data Set (24 items) on all clinical trials, and the public accessibility of that information.

UTN (Universal Trial Number assigned- similar to the NCT for the US ClinicalTrials.gov register/registry)

9www.who.int/ictrp/

Register.ClinicalTrials.gov

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BMC (BostonMC) 230 studies

BUMC (BostonU) 170 studies

CRC (BostonUCRC) about 60 studies-- PRS Administrator Cynthia Monahan (also CRC IRB Director)

ClinicalTrials.gov – Brief History

• ClinicalTrials.gov is a registry website maintained by the National Library of Medicine (NLM) at

the National Institutes of Health (NIH)

• ClinicalTrials.gov was launched in 2000 in response to FDA Modernization Act of 1997, which

required HHS, through NIH, to establish a clinical trials registry

• In 2005, International Committee of Medical Journal Editors (ICMJE) began requiring trial

registration as a condition of publication• In June 2007 the ICMJE adopted the WHO's definition of clinical trial: “Any research study that prospectively

assigns human participants or groups of humans to one or more health-related interventions to evaluate the

effects on health outcomes.“

• In 2008, ClinicalTrials.gov released its results database in response to the FDA Amendments Act

of 2007 (FDAAA), which expanded the requirements to include result reporting for trials involving

FDA regulated products

• Effective January 1, 2014, CMS required mandatory reporting of NCT on claims for items and

services provided in clinical trials that are qualified for coverage under the Medicare Clinical Trial

Policy (“Qualifying Clinical Trials”)

• In 2014 NIH expanded the definition of CTs

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ClinicalTrials.gov – brief history (cont.)

• On September 16, 2016, HHS issued the final rule for Clinical Trials Registration and Results

Information Submission, which clarified and expanded the registration and results submission

requirements in accordance with FDAAA (the “Final Rule”)https://www.federalregister.gov/documents/2016/09/21/2016-22129/clinical-trials-registration-and-results-

information-submission

• On September 16, 2016, NIH published a Policy, which requires registration and result reporting of all

NIH funded clinical trials (the “NIH Policy”) https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-

149.html NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information

• The NIH Policy complements the Final Rule

• Both the Final Rule and the NIH Policy went into effect January 18, 2017

• Noncompliance enforcement began April 18, 2017

• Upgrades to the ClinicalTrials.gov system continue• June 6, 2017- IPD (Individual Participant Data) Sharing Statement module was added to the Protocol Section to

document the plan for sharing and supporting materials.

• June 29, 2017- The new Document Section requires uploading of the Study Protocol and Statistical Analysis

Plan (SAP) as part of results information submission for studies with a Primary Completion Date on or after

January 18, 2017. Informed Consent Forms (ICF) may optionally be uploaded.

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What is a Clinical Trial Under the NIH Policy?

“A research study in which one or more human subjects are prospectively

assigned to one or more interventions (which may include placebo or other

control) to evaluate the effects of those interventions on health-related

biomedical or behavioral outcomes.”

• Includes clinical trials that are not “Applicable Clinical Trials”

Phase 1 trials of FDA-regulated drugs and biologicals

Small feasibility studies of FDA-regulated device products

Study of an intervention that is not regulated by the FDA (i.e. behavioral

interventions)

https://grants.nih.gov/grants/guide/notice-files/NOT-OD-16-149.html

NIH Clinical Trial Decision Tree

If yes to all of the following, registration and results reporting is required

1. Does the study involve human participants?

2. Are the participants prospectively assigned to an intervention?

3. Is the study designed to evaluate the effect of the intervention on the

participants?

4. Is the effect that will be evaluated a health-related, biomedical, or

behavioral outcome?

Does not include observational and natural history studies

“NIH Policy on Dissemination of NIH-Funded Clinical Trial Information” Presentation to the Clinical Trials Registration

Taskforce, December 15, 2016 by Sarah Carr and Valery Gordon

https://research.uic.edu/sites/default/files/Carr_Gordon_NIH.pdf

Is this a clinical trial?

1. Does the study involve human participants? Yes, the study involves human participants.

2. Are the participants prospectively assigned to an intervention? Yes, the participants are

prospectively assigned to receive an intervention, the investigational drug or placebo.

3. Is the study designed to evaluate the effect of the intervention on the participants? Yes, the

study is designed to evaluate the effect of the investigational drug on the participants’ symptoms.

4. Is the effect being evaluated a health-related biomedical or behavioral outcome? Yes, the

effect being evaluated, relief of symptoms, is a health-related outcome.

This study is a clinical trial.

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The study involves the recruitment of research participants with

disease X to receive either an investigational drug or a placebo. It is

designed to evaluate the efficacy of the investigational drug to relieve

disease symptoms.

Is this a clinical trial?

1. Does the study involve human participants? Yes, the study involves human participants.

2. Are the participants prospectively assigned to an intervention? Yes, the participants are

prospectively assigned to an intervention, measurement of an antibody level, with the idea that

knowledge of that antibody level might affect clinical management.

3. Is the study designed to evaluate the effect of the intervention on the participants? Yes, the

study is designed to evaluate how knowledge of the level of an antibody might inform treatment.

4. Is the effect being evaluated a health-related biomedical or behavioral outcome? Yes, the

effect being measured, how blood antibody levels inform treatment, is a health-related outcome.

This study is a clinical trial.

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The study involves the recruitment of research participants with disease X to

be evaluated with an investigational in vitro diagnostic device (IVD). The

study is designed to evaluate how knowledge of certain antibody levels

impacts clinical management of disease.

Is this a clinical trial?

1. Does the study involve human participants? Yes, the study involves human participants.

2. Are the participants prospectively assigned to an intervention? No, in this context the IVD

would not be considered an intervention. The IVD is being used to test its ability to measure

antibody levels, but not to test its effects on any health-related biomedical or behavioral outcomes.

This study is not a clinical trial.

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The study involves the recruitment of research participants with disease X to

test an investigational in vitro diagnostic device (IVD). It is designed to

evaluate the ability of the device to measure the level of an antibody in blood.

Is this a clinical trial?

1. Does the study involve human participants? Yes.

2. Are the participants prospectively assigned to an intervention? Yes, the participants are

prospectively assigned to different interference conditions.

3. Is the study designed to evaluate the effect of the intervention on the participants? No, the

purpose of these preliminary or practice runs is to evaluate and refine the study procedures, not

the effect of the intervention on the participants.

This study is not a clinical trial.

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Prior to a study of the effects of interference on working memory and brain function, an

investigator wishes to test the study procedures and adjust the difficulty of the memory tasks

for a range of individuals. To do so, the investigator runs a few healthy volunteers through the

procedures and adjusts and finalizes the procedures prior to initiating the formal study.

Health-related biomedical or behavioral outcome

Definition: the pre-specified goal/s or condition/s that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life. Examples include:

•positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression)

•positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers)

• reading comprehension and /or information retention)•positive or negative changes to disease processes•positive or negative changes to health-related behaviors•positive or negative changes to quality of life

Clarification-• If procedures and tasks are being performed to measure and describe, but not to modify then the

study is NOT a clinical trial

• Refer to case study # 18 a-f at: https://grants.nih.gov/policy/clinical-trials/case-studies.htm

Which Trials Require Results Information

• Applicable Clinical Trials (ACT) under FDAAA (The Final Rule)

– Studies with a Primary Completion Date on or after January 18, 2017,

results information required regardless of whether FDA regulated product

has been approved, licensed or cleared for marketing

– Primary Completion Date is “the date that the final subject was

examined or received an intervention for the purposes of final collection of

data for the primary outcome, whether the clinical trial concluded

according to the pre-specified protocol or was terminated.”

• NIH-funded clinical trials initiated (enroll first subject) after January 17,

2017 that are supported from grants submitted after that date.

What is an ACT? Use The ACT Check List

If “Yes” is answered to all 4 questions, and the study was initiated on or after January 18, 2017, the trial would meet the definition of an ACT.

International Committee of Medical Journal Editors (ICMJE)

• The ICMJE defines a clinical trial as any research project that prospectively assigns people

or a group of people to an intervention, with or without concurrent comparison or control

groups, to study the relationship between a health-related intervention and a health

outcome. • Health-related interventions are those used to modify a biomedical or health-related outcome;

examples include drugs, surgical procedures, devices, behavioural treatments, educational

programs, dietary interventions, quality improvement interventions, and process-of-care changes.

• Health outcomes are any biomedical or health-related measures obtained in patients or

participants, including pharmacokinetic measures and adverse events.

• The ICMJE does not define the timing of first participant enrollment, but best practice dictates

registration by the time of first participant consent.

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• The ICMJE recommends that journals publish the trial registration number at the end of the

abstract. The ICMJE also recommends that, whenever a registration number is available, authors

list this number the first time they use a trial acronym to refer either to the trial they are reporting or

to other trials that they mention in the manuscript.

International Committee of Medical Journal Editors (ICMJE)

• The purpose of clinical trial registration is to prevent selective publication and selective

reporting of research outcomes, to prevent unnecessary duplication of research effort,

to help patients and the public know what trials are planned or ongoing into which they

might want to enroll, and to help give ethics review boards considering approval of new

studies a view of similar work and data relevant to the research they are considering.

• Retrospective registration, for example at the time of manuscript submission, meets

none of these purposes. Those purposes apply also to research with alternative

designs, for example observational studies. For that reason, the ICMJE encourages

registration of research with non-trial designs, but because the exposure or

intervention in non-trial research is not dictated by the researchers, the ICMJE does

not require it.

• The ICMJE recommends that journals publish the trial registration number at the end

of the abstract. The ICMJE also recommends that, whenever a registration number is

available, authors list this number the first time they use a trial acronym to refer either

to the trial they are reporting or to other trials that they mention in the manuscript.

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Registration and Results Reporting Requirements on ClinicalTrials.gov

ICMJE Policy (effective 2005 updated 2017). Registration required for all phases of clinical

trials of all interventions with any funding source prior to enrollment of the first participant.

Enforcement is refusal to publish.

Element Final rule NIH Policy

Intervention and

phase type

Drug, biologic, device products regulated by FDA;

not phase 1

All, including behavioral

interventions; all phases

Timeframe-

registration

Not later than 21 days after enrollment of the first

subject

At BMC/BUMC BEFORE IRB approval

Same

Registration data

elements

Consists of descriptive information, recruitment

information, location and contact information, and

administrative data.

Same

Timeframe- results

reporting

Not later than 12 months after primary completion date Same

Results data

elements

Includes participant flow, demographic and baseline

characteristics, outcomes and statistical analyses,

adverse events, the protocol and statistical analysis

plan, and administrative information

Same

Effective Date Jan 18, 2017; Compliance by April 18, 2017 Jan 18, 2017

Source: https://www.nih.gov/news-events/summary-table-hhs-nih-initiatives-enhance-availability-clinical-trial-information

ICMJE Data Sharing Policy

1. As of July 1, 2018 manuscripts submitted to ICMJE journals that report the results of

clinical trials must contain a data sharing statement.

2. Clinical trials that begin enrolling participants on or after January 1, 2019 must include a

data sharing plan in the trial's registration.

3. If the data sharing plan changes after registration this should be reflected in the statement

submitted and published with the manuscript, and updated in the registry record.

4. Authors of secondary analyses using shared data must attest that their use was in

accordance with the terms (if any) agreed to upon their receipt.

• They must also reference the source of the data using its unique, persistent identifier to provide

appropriate credit to those who generated it and allow searching for the studies it has supported.

• Authors of secondary analyses must explain completely how theirs differ from previous analyses.

• In addition, those who generate and then share clinical trial data sets deserve substantial credit for

their efforts. Those using data collected by others should seek collaboration with those who

collected the data. As collaboration will not always be possible, practical, or desired, the efforts of

those who generated the data must be recognized.

• http://www.icmje.org/news-and-editorials/data_sharing_june_2017.pdf

26

Responsible Party’s (RPs) Obligations under the Final Rule and the NIH Policy

• Register the clinical trial

– Final Rule + NIH Policy no later than 21 days after enrollment

– For ICMEJE prior to the enrollment of first participant

▫ BMC/BUMC Policy Requires that all CTs be registered (obtain the NCT) before the IRB review

will be completed

– For QCT (those that submit claims to CMS) prior to enrollment of first participant

• Update the clinical trial (at least annually [prefer every 6 months] and as needed)

For Final Rule and NIH Policy update on at least once every 12 months (some information

within 15 or 30 days of change-- recruitment status, Primary Completion Date)

• Report results of ACT and NIH funded clinical trials

For Final Rule and NIH Policy, submit summary results, which includes adverse events

information, not later than 12 months after the Primary Completion Date (delays allowed under

certain circumstances)

• Summary

ALL CTs must be registered and updated as needed and at least annually

Results must be reported on all ACTs and any NIH grant with enrollment and funding after Jan

17, 2017

Required CT Results Information for ACTs and NIH Funded Clinical Trials

• Participant Flow

• Demographic and baseline characteristics

• Outcomes and statistical analyses

• Adverse event information

• Protocol and statistical analysis plan (new requirement)

• Administrative information

• Additional information for applicable device clinical trials of unapproved or

uncleared devices

Review instructions and the templates before the trial starts to make sure the data

is collected to facilitate compliance with the results information requirements

Navigating register.clinicaltrials.gov

(dashboard, protocol, results, and

documents sections)

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PRS- Protocol Registration and Results System

To obtain a ClinicalTrials.gov user account, contact your institutional CTgov administrator.

You will be assigned a username (case/space sensitive) and CTgov will email instructions on how to set your

password. Your/the RP/PR’s password can be reset as needed, just contact the PRS Administrator.

The organization name will be either BostonMC or BostonU

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32

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Definitions from CTgov

Completion Dates are based on data collection. They are NOT based on:

• data analysis

• publication

• IRB closure

If a date is ‘anticipated’ only provide a month and year. If a date is ‘actual’ you need to provide

the full date.

Often the primary completion and the study completion date are the same but not always.

Remember to go back into the record and update all ‘anticipated dates before they become in

arrears or the it is an error and the record becomes a problem record.

If you use these as

Completion Dates, you may

have LATE RESULTS

Primary and Study Completion Dates

37

Group Activity

Editing Examples

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Study Status Section

What is the record verification date?

How often do records need to be verified?

What is the overall status?

What is the overall status if you have collected all study data on each

participant but you are still analyzing identifiable data? ‘active, not recruiting’

or ‘completed’?

What is the difference between the primary completion date and the study

completion date?

Can they be the same date?

What is the difference between the information provided for an ‘anticipated’

date and an ‘actual’ date?

What would you do if you ‘anticipated’ that the primary completion date

would be December 2019 but the ‘actual’ primary completion date turned out

to be November 12 , 2019?

Once the overall status is ‘completed’ what other information needs to be

added to the record?

39

Study Status Section

What is the record verification date? From CTgov- the date (month and year) on which the responsible

party last verified the clinical study information in the entire ClinicalTrials.gov record for the clinical study, even if

no additional or updated information is being submitted.

How often do records need to be verified? A minimum of once a year although CTgov prefers at least

twice a year.

What is the overall status? From CTgov- the recruitment status for the clinical study as a whole, based upon

the status of the individual sites. If at least one facility in a multi-site clinical study has an Individual Site Status of

"Recruiting“ or “Enrolling by invitation”, then the Overall Recruitment Status for the study must be "Recruiting" or

“Enrolling by invitation”.

What is the overall status if you have collected all study data on each participant but you

are still analyzing identifiable data? ‘active, not recruiting’ or ‘completed’? If all study data has

been collected on each participant then the study is ’completed’; you can continue to analyzed identifiable data

for as long as you need to. “completed’ refers to recruitment not to the research study and is defined by CTgov

as: the study has concluded normally; participants are no longer receiving an intervention or being examined

(that is, last participant’s last visit has occurred).

40

Study Status Section continued

What is the difference between the primary completion date and the study completion

date? From CTgov-

Primary Completion Date is the date that the final participant was examined or received an intervention for the

purposes of final collection of data for the primary outcome, whether the clinical study concluded according to

the pre-specified protocol or was terminated. In the case of clinical studies with more than one primary outcome

measure with different completion dates, this term refers to the date on which data collection is completed for

all of the primary outcomes.

Once the clinical study has reached the primary completion date, the responsible party must update the Primary

Completion Date to reflect the actual primary completion date.

Study Completion Date is the date the final participant was examined or received an intervention for purposes of

final collection of data for the primary and secondary outcome measures and adverse events (for example, last

participant’s last visit), whether the clinical study concluded according to the pre-specified protocol or was

terminated.

Once the clinical study has reached the study completion date, the responsible party must update the Study

Completion Date to reflect the actual study completion date.

Can they be the same date? Yes and most of the time they are unless there is an intervention or data

collection for secondary outcome measures that occurs after the primary outcome measures are collected eg a

two year follow up survey or additional blood draw, BP, etc

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Study Status Section continued

What is the difference between the information provided for an ‘anticipated’ date and an

‘actual’ date? An ‘anticipated’ date is the projected month and year when an event is expected. Do not

provide a day, as if you provide just the month and year then the record will remain up to date until the end of

the month (eg if you gave an ‘anticipated’ study start date of April 10, 2020 then on April 11, 2020 if it is not

edited to ‘actual’ it will be an error. In contrast, if the ‘anticipated date was April 2020, then the record is up to

date until the last day in April but on May 1 an error message will appear unless the ‘actual’ date [which is a full

date including the month, day and year] is entered.

What would you do if you ‘anticipated’ that the primary completion date would be

December 2019 but the ‘actual’ primary completion date turned out to be November 12,

2019? Just go into the record and edit the primary completion date from December 2019 to the ‘actual’ date

of November 12, 2019 and then release the record for PRS review. Remember if you make edits but do not

release the record for PRS review is as if the edits were never made. You will see them on your institutional

CTgov database/registry but they won’t appear on the public clinicaltrials.gov registry until reviewed and

released by CTgov.

Once the overall status is ‘completed’ what other information needs to be added to the

record? You will need to go into the Study Enrollment section and change the ‘anticipated’ enrollment to the

‘actual’ enrollment as if the overall status is ‘completed’ you are no longer enrolling/recruiting participants for

the study.

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Outcome Measures

What three pieces of information are required for each outcome measure?

How many primary outcome measures and secondary outcome measures can

you list?

If you are doing a study and depressive symptoms are to be collected using the

Beck Inventory at baseline, 3mo and 6mo, propose an outcome measure title,

a description and a time frame for the outcome measures

If you are doing a study and quarterly patient satisfaction is a primary outcome

measure to be collected based on a survey, what title, description and time

frame would you propose.

What would you do if your outcome measures change during the study?

43

Outcome Measures

What three pieces of information are required for each outcome measure? A title- a

name of the specific outcome measure and how it will be assessed, a detailed description of that measure including

how you would interpret results [eg are lower or higher scores more favorable], and the timeframe for collecting the

outcome measure.

How many primary outcome measures and secondary outcome measures can

you list? You can have as many of each as you need and you can also include additional pre-specified outcome

measures. The number and types of outcome measures will be determined by your study protocol.

If you are doing a study and depressive symptoms are to be collected using the

Beck Inventory at baseline, 3mo and 6mo, propose an outcome measure title,

a description and a time frame for the outcome measuresTitle- Change in depressive symptoms based on the Beck Depression Inventory

Description- The Beck Depression Inventory (BDI) is a 21 question multiple-choice self report questionnaire where each

responses ranging in intensity from little or none to severe and are scored with a value of 0 to 3. The possible range of

scores is 0 to 63. Standard cut-offs are 0 to 9= minimal depression; 10 to18= mild depression; 19 to 29= moderate

depression; and 30 to 63= severe depression.

Time frame- baseline, 3 months, 6 months

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Outcome Measures continued

If you are doing a study and quarterly patient satisfaction is a primary outcome

measure to be collected based on a survey, what title, description and time

frame would you propose. You would need a very specific title (eg Patient satisfaction based on a self

report survey), a detailed description of the survey- number of items, range of responses (such as 1= strongly agree

to 5=strongly disagree), the overall potential range of values and whether lower or higher scores are more favorable)

and you would need to copy this outcome [using the ‘copy outcome function] for each time frame (eg one for 3 months,

one for 6 months, one for 9 months, and one for 12 months)

What would you do if your outcome measures change during the study? Since you are

doing human subjects/clinical research changes in the protocol are expected so remember anytime a non-personnel

amendment is submitted to your IRB to review the your CTgov record (and change the record verification date to that

month and year) and make any needed edits including any affecting the outcome measures. If an outcome measure

changes, edit it as needed which may involve changing the title, the description, and the timeframe or maybe just one

or two of those sections. Then remember to always have the RP (responsible party)/PI or the sponsor release the

record for CTgov PRS review.

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Tips for Registering, Updating and

Reporting Results onClinicalTrials.gov

46

Some CTgov Tips

• All ERRORS and Major Comments (in pink) must be addressed in a timely

manner

• You can ignore Warnings and Advisory Comments (in light orange)

• You can ignore Red flags on the overall record

• Do not use pronouns any where in the record (e.g. ‘the investigators’ instead

of ‘our research team’)

• Use the ‘spelling check’ on the dashboard before submitting to PRS review

• Set up a tickler system for annual verification and for updating all

‘anticipated” dates

• Note the each time the record is released for PRS review a PDF is made

and attached and a log of all traffic on the record

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Some Additional Tips

• Each time you submit an amendment and/or the annual review to the IRB, revise

your protocol, modify your outcome measures, or have other changes to the

research (egg early termination of the study) go into your record and edit as

needed

• If you have to report results meet with the PRS Administrator (months in advance)

to review the tables, format and requirements for statistical testing.

• Before you begin to add results check your outcome measures and make sure they

are what you plan to report about as they flip to the results section.

• Submit results as soon as possible and within a year of the primary completion

date (records can become ‘late results per FDAAA’ during the review period)

• Respond to PRS Administrator comments promptly

• The public has full access to the posted information including changes that are

made to the record so keep the record up to date, accurate and consistent with the

research study.

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NIH Policy for Noncompliance

• Requirements for clinical trial registration and results submission will be

included in the terms and conditions of the award

• Must certify compliance with registration and results requirements in

progress report forms

• Failure to comply with terms and conditions of award may provide basis

for enforcement actions (45 C.F.R. 75.371 – Remedies for

noncompliance for HHS awarding agency or pass-through entity)

– Temporarily withhold payments pending correction

– Suspend or terminate award

– Withhold further awards for the project or program

NIH-Funded ACT and Final Rule Noncompliance

• If NIH-funded clinical trial is also an ACT, non-compliant with 42 USC

282(j) (FDAAA) and 42 CFR Part 11.66 (Final Rule)

– HHS agency will verify compliance, and if not compliant, any remaining

funding for grant or funding for a future grant to such grantee will not be

released

– If HHS agency will provide notice to grantee of non-compliance and

allow 30 days to correct

• ACT (Applicable Clinical Trial)

– Failure to certify compliance and failure to submit required information

are violations of Food, Drug and Cosmetic Act

– Civil monetary penalties of up to $11,800+/day

– Institutions had until April 17, 2017 to become compliant

Resources

• https://clinicaltrials.gov/

• www.bumc.bu.edu/ohra/clinicaltrials-gov/

• www.nih.gov/news-events/news-releases/hhs-take-steps-provide-more-information-about-clinical-trials-

public

• www.nih.gov/news-events/news-releases/hhs-take-steps-provide-more-information-about-clinical-trials-

public

• Zarin DA, et al. “Trial Reporting in Clinical Trials.gov– The Final Rule”. NEJM 2016,375:20, 1998-2004.

www.nejm.org/doi/full/10.1056/NEJMsr1611785

• Tse T, Bergeris A, Zarin DA. Lockbox for Registered Trials of Unapproved Devices. N Engl J Med. 2018

March 15;378(11):1064.

• Bergeris A, Tse T, Zarin DA. Trialists' intent to share individual participant data as disclosed at

ClinicalTrials.gov. JAMA. 2018 Jan 23;319(4):406-8.

• www.nih.gov/news-events/summary-hhs-nih-initiatives-enhance-availability-clinical-trial-information

• http://www.bu.edu/researchsupport/2017/08/31/new-nih-requirements-for-registering-nih-funded-clinical-

trials-on-clinicaltrials-gov-and-for-good-clinical-practice-gcp-

training/?utm_source=RR&utm_medium=email&utm_campaign=0917

• The hidden side of CTs-- https://www.youtube.com/watch?v=-RXrGLolgEc&feature=youtu.be

Site Specific Policies

52

Process AT BMC – BU Medical Campus

• Provide centralized support through the BMC – BU Medical Campus Office of

Human Research Affairs (OHRA)

• Process is documented in a joint policy

• Studies to Register

▫NIH-Funded Clinical Trials (results information needed)

▫Applicable Clinical Trials (ACT) (results information needed)

▫Qualifying Clinical Trials (QCT) (those that submit claims to CMS)

▫Clinical trials Meeting ICMJE Definition

• Above studies should be registered in ClinicalTrials.gov concurrently with IRB

submission

• NCT number must be provided to IRB and BMC CTO for trials using BMC

clinical infrastructure

Process at BMC – BU Medical Campus

• BMC and BU Medical Campus each delegate PI as RP

• Departing PIs will need a transition plan for ongoing studies in ClinicalTrials.gov

• Registration through the PRS (Protocol Registration and Results System)

institutional administrator

▫Karla Damus for both BMC and BU Medical Campus, if unavailable:- Fanny Ennever for BMC

- Mary-Tara Roth for BU Medical Campus

• BMC non-compliance escalated to BMC Research Compliance officer then to

BMC Institutional Official

• BU Medical Campus non-compliance escalated to Director, Human Research

Protection Program, OHRA

• Training, education, and compliance monitoring will be provided by

OHRA/CRRO/CTSI

Who is Responsible for Registering, Updating and Submitting Results?

• The Responsible Party is the awardee or investigator for NIH-funded

clinical trial (subawardees and subinvestigators must coordinate with RP)

• When BMC or BU Medical Campus is the sponsor (no outside funding,

NIH grantee) they will designate the PI as RP

- To be the RP the PI must

Be responsible for conducting the trial

Have access to and control over the trial data

Have the right to publish the trial results; and

Have the ability to meet the ClinicalTrials.gov requirements for

submitting and updating trial information

Supporting Researchers with the Process at BMC–BU Medical Campus

• Assist PIs in determining if their study is a CT and the type of trial

• Assist in registration, updating and reporting results

• Regular auditing and monitoring for compliance

• Training and education for RPs/PIs and research staff provided by

OHRA/CRRO

– Annually, present a CRRO Seminar on ClinicalTrials.gov

– Integrate key information into CRRO trainings (PI and Fundamentals)

– Educational venues developed for BMC/BU Medical Campus Research

Professional Network (RPN) and the BMC Research Managers

– Departmental presentations to research faculty on request

– Website with ClinicalTrials.gov information, links, and resources (e.g.

checklists, algorithms, templates, videos, publications)

– CRRO consultations from the design of clinical trials throughout the

registration, updating and results reporting process

Contact Karla Damus damusk@bu.edu, 358 7283

Contacts

Karla Damus

Administrator, ClinicalTrials.gov BMC/BU Medical Campus

358 7382

damusk@bu.edu

Fanny Ennever

BMC Research Compliance Officer

638-8874 fanny.ennever@bmc.org

Mary-Tara Roth

Director, CRRO

358 7679

mtroth@bu.edu